Transcriptomic Analysis Links Eosinophilic Esophagitis and Atopic Dermatitis

Frontiers in Pediatrics

Sébastien Holvoet¹  Marc E. Rothenberg¹  Joseph D. Sherrill¹  Gurjit K. Khurana Hershey²  Francis Foata³  Rémi Doucet-Ladevèze³  Carine Blanchard³  Frédéric Raymond³ 

[1] Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, United States;Division of Asthma Research, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, United States;Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland;

关键词: asthma;    atopic dermatitis;    eosinophilic esophagitis;    epithelial cells;    interleukin 13;   

DOI  :  10.3389/fped.2019.00467

来源: DOAJ

【 摘 要 】

Background: Eosinophilic esophagitis (EoE) is commonly associated with concomitant atopic diseases including atopic dermatitis (AD) and allergic airway (AA) diseases including asthma. Despite this link and the shared pathologic features across these three disorders, detailed analyses of the unifying molecular pathways are lacking.Objectives: We sought to investigate the mRNA expression profile overlap between EoE, AA, and AD and to identify the involvement of interleukin 13 (IL-13) in modulating gene expression.Methods: Whole-genome mRNA expression analyses were performed on tissue specimens (biopsies or nasal brushes) from patients with EoE, AD, and AA, and IL-13-stimulated primary human epithelial cells from the esophagus, the skin, and the airways.Results: By human disease expression profiles, EoE evidenced a significantly higher overlap (p = 0.0006) with AD (181 transcripts; 10%) than with AA (124 transcripts, 7%). Only 18 genes were found to be commonly dysregulated among the three diseases; these included filaggrin, histamine receptor H1, claudin 1, cathepsin C, plasminogen activator urokinase receptor, and suppressor of cytokine signaling 3. Ontogenetic analysis revealed a common immune/inflammatory response among the three diseases and a different epithelial response (epidermal cell differentiation) between EoE and AA. The overlap between the IL-13–stimulated epithelial cell transcriptome and the respective disease transcriptome was 22, 9, and 5% in EoE, AD, and AA, respectively, indicating a greater involvement of the IL-13 pathway in EoE than AA (p = 0.0007) or AD (p = 0.02).Conclusion: EoE, AD, and AA share a common set of disease-specific transcripts, highlighting common molecular etiology. Their comparative analysis indicates relatively closer relationships between EoE and AD, particularly centered around IL-13–driven pathways. Therefore, these findings provide an increased rationale for shared therapeutic strategies.

【 授权许可】

Unknown